Thromboxane A2 and prostaglandin endoperoxide analogue effects on porcine renal blood flow.
Thromboxane A2 (TxA2) has been implicated as a mediator of renal and cardiovascular diseases. However, the direct effects of TxA2 on the renal system have been difficult to study because of the instability of the agonist. In the present study injection of synthetic TxA2 directly into the renal artery of anesthetized pigs produced dose-related decreases in renal blood flow (RBF) from 101 +/- 11 to 12 +/- 3 ml/min at the highest dose (20 ng/kg). The reductions in RBF were similar to those produced by the stable prostaglandin endoperoxide analogue, U-44069, although TxA2 was three times more potent. Under these conditions there were no effects on either mean (MAP) or pulmonary arterial pressures (PAP), or the heart rate (HR). The maximal effects produced by TxA2 and U-44069 on RBF were reproducible and the response remained unchanged after pretreatment with either heparin or indomethacin. Systemically administered TxA2 (200 ng/kg iv) increased PAP from 20 +/- 1 to 34 +/- 3 mmHg and this effect was associated with modest increases in MAP and HR. Intravenous administration of the thromboxane receptor antagonist, L-655,240, inhibited the reductions in RBF produced by intrarenal TxA2 and U-44069 and attenuated the cardiopulmonary effects of TxA2 administered intravenously. The results demonstrate directly that TxA2 is a potent agent for decreasing RBF through interaction with a thromboxane receptor.
Cirino
M
M
Department of Pharmacology, Merck Frosst Centre for Therapeutic Research, Quebec, Canada.
Morton
H
H
MacDonald
C
C
Hadden
J
J
Ford-Hutchinson
A W
AW
D000818:Animals; D006439:Hemodynamics / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology; D007267:Injections; D007668:Kidney; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D012079:Renal Circulation / Q000187:drug effects*; D013552:Swine; D013928:Thromboxane A2 / Q000494:pharmacology*; D013931:Thromboxanes / Q000037:antagonists & inhibitors
D007211:Indoles; D011450:Prostaglandin Endoperoxides, Synthetic; D013931:Thromboxanes; C052517:L 655240; C028429:U 44069; D013928:Thromboxane A2